Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice

Abstract

Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specialist visits were collected. A mouse model of osteomyelitis was used to verify the presence of impaired glucose metabolism and depression. All data were processed by SPSS. Results: The incidence of T2DM was 2.37-fold higher in patients with COM than in those without. In COM patients, subjects with T2DM (DDM) had higher BMI, less exercise and more frequent visits to specialists than those without (Con). Glucose and lipid metabolism were worse in patients with DDM. Patients with DDM had higher levels of white blood cells (12.9±2.1×109/L vs. 11.7±2.2×109/L, p=0.027), CRP (28.4±4.5 mg/L vs. 22.0±4.8 mg/L, p<0.001), TNF-α (13.5±5.0 pg/mL vs. 9.4±2.6 pg/mL, p= 0.003) and IL-6 (12.9±3.2 pg/mL vs. 9.2±2.7 pg/mL, p<0.001). Significantly increased fasting blood glucose concentrations and impairment of oral glucose tolerance tests were also observed in mice modelling osteomyelitis, which were accompanied by elevated TNF-α and IL-6 levels. Furthermore, the proportion of depression (63.2% vs. 35.2%, p=0.003) and severe anxiety (31.6% vs. 9.1%, p=0.002) were significantly higher in the DDM group. Osteomyelitis mice showed obvious depressive-like behaviours. The levels of TNF-α, IL-6, CRP, BMI, and LDL; lack of exercise; SAS; HAQ; and SF36 assessment were risk factors for the development of T2DM in COM patients. Conclusions: Chronic osteomyelitis increased the incidence of T2DM in both humans and mice. Inflammation, mental illness and lack of exercise were risk factors for the occurrence of T2DM in osteomyelitis. Comprehensive consideration of patient history, including metabolism and mental health, is needed in planning future treatment.

Keywords: chronic osteomyelitis; diabetes; inflammation; insulin resistance; mental health.; risk.

Figure 1

The Kaplan-Meier curves of the diabetes-free rates in patients with and without chronic osteomyelitis

Figure 2

The number of subjects who developed diabetes in chronic osteomyelitis

Figure 3

The correlation between fasting blood glucose and potential risk factors. The correlation between fasting blood glucose and BMI (A), total cholesterol (B), white blood cells (C), C-reactive protein (D), tumour necrosis factor α (E) and interleukin-6 (F).

Figure 4

The correlation between HOMA-IR and potential risk factors. The correlation between HOMA-IR and BMI (A), C-reactive protein (B), tumour necrosis factor α (C) and interleukin-6 (D).

Figure 5

The correlation between HbA1c and potential risk factors. The correlation between HbA1c and BMI (A), white blood cells (B), C-reactive protein (C), tumour necrosis factor α (D) and interleukin-6 (E).

Figure 6

The metabolic and inflammatory indicators in the mouse model of osteomyelitis. A, representative X-ray images of the mouse model of osteomyelitis (COM) and sham-operated mice (Sham). B, body weight of mice in Sham and COM. C, the level of fasting blood glucose in mice in Sham and COM. **, p<0.01. D, oral glucose tolerance test in mice in Sham and COM. **, p<0.01. E, serum level of tumour necrosis factor α (TNF-α) in mice in Sham and COM. **, p<0.01. F, serum level of interleukin-6 (IL-6) in mice in Sham and COM. **, p<0.01.

Figure 7

The depression-like behaviours in the mouse model of osteomyelitis. A, representative types of travel strategies in the open field test of mice in Sham and COM. B, the travel distance of mice in Sham and COM. C, the time spent in the centre area of mice in Sham and COM. D, the immobility time in the tail suspension test of mice in Sham and COM. E, the immobility time in the forced swimming test of mice in Sham and COM. **, p<0.01.